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Based on extended theory of Derjaguin, Landau and Overbeeck (xDLVO) concerning aggregation of colloids and biological cells it was hypothesized that platelet antiaggregant agents have to reduce the aggregation of erythrocytes also. Applying Einstein-Stokes theory of sedimentation of spheres in viscous media it was concluded that sedimentation of erythrocytes is in fact sedimentation of aggregates of the approximately same size. Consequently, an expected outcome was that addition of antiaggregants in vitro to blood samples from patients with rheumatic or cardiovascular diseases will be the decrease of erythrocytes sedimentation. Starting from usual practice of dual antiaggregant therapy (aspirin and clopidogrel) effects of clopidogrel were compared with effects of clopidogrel plus small concentrations of aspirine and dipyridamole (smaller that their concentrations in plasma after in vivo administration) in order to put in evidence a possible synergic effect at platelet membrane level. Whole blood (0.8ml) was collected on 0.1ml 1% EDTA and then was added 25 or 50μl normal saline solution of clopidogrel or of the combination acetylosalycilic acid, clopidogrel and dypyridamole. The final concentrations were 1, 2 and μg/ml, of the same order as cumulated concentration of clopidogrel and its metabolites in clinical pharmacokinetics. Experiments were performed on a number of 40 human blood samples obtained from 2 groups of 20 patients. Sedimentation of erythrocytes was recorded using a camera and captured data were stored on a computer. Global analysis evidenced that in presence of antiaggregants the clusters of the sedimentation curves shifted down and into right, indicating a decrease and delay of sedimentation. Initial slopes and extent of sedimentation decreased linearly on clopidogrel concentration within the 1-3μg/ml range. For comparison of mean curves corresponding to different clopidogrel concentrations it was applied a metric from biopharmacy: areas under plasma concentrations curves (AUC) of drugs. The areas under average sedimentation curves decreased linearly at clopidogrel concentration within the 1-3μg/ml range. The same experiments were performed and similar results were obtained with the triple antiaggregant combination (clopidogrel, acetylosalycilic acid and dipyridamole). Apparently, a synergism between the tested antiaggregants appeared at studied concentration but the number of data was not sufficient to prove the statistical significance of the difference between clopidogrel alone and in triple combination. [ABSTRACT FROM AUTHOR]

In context of Evidence Based Medicine concept, Good Clinical Practice rules specify that "data generated should be reliable and robust". Reliability and robustness are further translated in requirements concerning statistical and clinical significance of results. Paper presents main aspects connected with comparison of evolutions of endpoints as function of different parameters like time, administered dose, proportion of active components etc., leading to problems of comparison of curves, with direct application to comparison of platelets aggregation curves in presence of different concentrations of ionic calcium. Theoretical part presents comparison of curves in biopharmacy using f2 metric and area under curve metric, and comparison of survival curves in clinical studies. Platelet aggregation test was performed using Born turbidimetric light transmission method using Helena PACKS-4 Aggregometer. Blood samples were collected from patients in internal medicine ward of Colentina Clinical Hospital. Platelet rich plasma (PRP) was obtained by centrifugation at 200G. Washed platelets where extracted by centrifugation of PRP at 2700 G. The supernatant was replaced with sodium chloride 0.9%. Platelets aggregation was induced by adding different concentrations of calcium gluconate into cuvettes which contained washed platelets. After digitalization, curves were compared using similarity factor f2 and areas under curves. Paper puts in evidence that both type of comparison, after mathematical and statistical evaluation, have to define a clinical threshold for clinical significance. In case of f2, in dissolution studies the threshold is 10%, in case of bioequivalence based on area under curves threshold is 20%. Establishment of the threshold for significant clinical difference in comparison of aggregation curves is not only a problem of statistics. Graphical representation of data suggested significant differences between curves obtained with different concentrations of calcium ion. Application of both f2 method and log-rank test let to conclusion that differences were statistical significant. Representation of aria under curves as function of calcium concentration put in evidence an approximate linear dependence. In spite of apparently objective character of mathematical approach, the problem of comparison of aggregation curves remains practically unsolved since we do not know the threshold between clinical significant and non-significant results. [ABSTRACT FROM AUTHOR]

1980. aastate algul käivitunud soome ja eesti keele kontrastiivse uurimise projekti “Soome ja eesti keele grammatiline võrdlus” üks põhiülesandeid oli kahe keele süntaktilise struktuuri võrdlus. Eesti poolelt vaadatuna andis projekti raames toimunud teadussuhtlus rohkesti infot ja ideid eesti keele süntaksi uurijatele ja eesti keele teadusliku grammatika koostajatele. Soome ja eesti süntaktilise struktuuri võrdluse seisukohalt oli siiski tegemist pigem ettevalmistava etapiga. Konkreetsete tulemusteni jõuti 1990. aastail, kui rahvusvahelises lingvistikas muutus üheks juhtivaks trendiks keeletüpoloogia. Turu ülikoolis algatatud jätkuprojekti “Läänemere piirkonna keelte grammatiline võrdlus” (SCLOMB) käigus loodi samanimeline korpus, mis kaasas soome ja eesti keele võrdlusesse ka nende kontaktkeeled. 1990. aastail ilmus hulk võrdlevaid artikleid, kusjuures eriti häid tulemusi saadi aspekti ja aja süsteemide võrdluses. Seni põhiliselt veaanalüüsi tulemusi käsitlev kogumik “Lähivertailuja” hakkas sisaldama ka struktuurivõrdlusi ning muutus teaduslikult kaalukamaks.

29. juulil 2010 sai 60-aastaseks Tartu ülikooli tänapäeva eesti keele professor Helle Metslang

Eesti kirjakeeles on viis vastandavat sidesõna: aga,kuid,ent,kuna ja vaid. Sidesõnu aga,kuid ja ent on peetud sünonüümideks. Tegelikult on aga üldvastandav sidesõna, mida on võimalik kasutada nii kontrastiivse (Mari on virk,aga Juku laisk) kui ka ootusvastase vastanduse puhul (Sajab,aga me lähme jalutama). Erinevalt teistest vastandavatest sidesõnadest on sidesõnal aga ka konnektiivpartikli omadusi –ta ei pruugi paikneda lause algul (Mari on virk,Juku aga laisk). Sidesõnad kuid ja enton mõlemad ootusvastast vastandust markeerivad sidesõnad (Sajab,kuid/ent me lähme jalutama), aga ent esineb keskmiselt seitse korda vähem kui kuid, kusjuures tema põhiliseks kasutusvaldkonnaks on ilukirjandus. Kontrastiivset vastandust võib markeerida ka kuna, kuid harva. Tänapäeval on kuna kasutusel ennekõike kausaalse sidesõnana. Korrigeeriva vastanduse markerina on üldlevinud vaid(Ma ei söö mitte saia,vaid leiba), sidesõnade aga,kuid ja ent kasutus on võimalik peamiselt siis, kui korrektsioonile lisandub mööndus (Saia ma ei söö,aga/kuid/ent leiba küll).

Recent advancements in the formulation of solid dosage forms involving active ingredient-cyclodextrin complexes have garnered considerable attention in pharmaceutical research. While previous studies predominantly focused on incorporating these complexes into solid states, issues regarding incomplete inclusion prompted the exploration of novel methods. In this study, we aimed to develop an innovative approach to integrate liquid-state drug-cyclodextrin inclusion complexes into solid dosage forms. Our investigation centered on rivaroxaban, a hydrophobic compound practically insoluble in water, included in hydroxypropyl-β-cyclodextrin at a 1:1 M ratio, and maintained in a liquid state. To enhance viscosity, hydroxypropyl-cellulose (2 % w/w) was introduced, and the resulting dispersion was sprayed onto the surface of cellulose pellets (CELLETS®780) using a Caleva Mini Coater. The process parameters were meticulously controlled, with atomization air pressure set at 1.1 atm and a fluidizing airflow maintained at 35-45 m 3 /h. Characterization of the coated cellets, alongside raw materials, was conducted using Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) analyses. Physicochemical evaluations affirmed the successful incorporation of rivaroxaban into hydroxypropyl-β-cyclodextrin, with the final cellets demonstrating excellent flowability, compressibility, and adequate hardness. Quantitative analysis via the HPLC-DAD method confirmed a drug loading of 10 mg rivaroxaban/750 mg coated cellets. In vitro dissolution studies were performed in two distinct media: 0.022 M sodium acetate buffer pH 4.5 with 0.2 % sodium dodecyl sulfate (mirroring compendial conditions for 10 mg rivaroxaban tablets), and 0.05 M phosphate buffer pH 6.8 without surfactants, compared to reference capsules and conventional tablet formulations. The experimental capsules exhibited similar release profiles to the commercial product, Xarelto® 10 mg, with enhanced dissolution rates observed within the initial 10 min. This research presents a significant advancement in the development of solid dosage forms incorporating liquid-state drug-cyclodextrin inclusion complexes, offering a promising avenue for improving drug delivery and bioavailability., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Evaluate the misuse of proton pump inhibitors (PPIs) in geriatric long-term care (LTC) patients and improve caregiving by de-prescribing non-relevant PPIs in this population., Aim: This study was conducted in the long-term care department of the geriatric hospital Pierre-Garraud in Lyon. All patients receiving PPI for more than 8 weeks were included. A reassessment form was filled to evaluate the treatment benefit/risk ratio during a collegial consultation between the patient's referring physicians and pharmacists. During these consultations, the following possible decisions were taken: continuation, dose adjustment or gradual discontinuation of treatment. Patients' monitoring were performed one month and three months after discontinuation to detect any relapses and causes., Results: Among the 113 patients included, 97 patients had their treatment re-evaluated by collegial consultation. Forty-four (45.4%) patients were treated in accordance with recommendations. For 24 of them, the indication was symptomatic recurrent gastroesophageal reflux disease. The treatment of more than half of the re-evaluated patients (54.6%) was gradually stopped. After the 3-month follow-up post-discontinuation, excluding patients who died during this period, 80.9% of the discontinuations were well-tolerated and only nine were resumed (19.1%)., Conclusion: This study allowed a re-evaluation of PPI treatments in a high-risk population and offered a decision support tool focused on the benefit/risk balance of PPIs; 55% of treatments were considered irrelevant and could be stopped with 80% of good tolerance., (Copyright © 2024 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Green chemistry is a pharmaceutical industry tool, which, when implemented correctly, can lead to a minimization in resource consumption and waste. An aqueous extract of Salix alba L. was employed for the efficient and rapid synthesis of silver/gold particle nanostructures via an inexpensive, nontoxic and eco-friendly procedure. The nanoparticles were physicochemically characterized using ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), X-ray diffraction (XRD) and scanning electron microscopy (SEM), with the best stability of up to one year in the solution obtained for silver nanoparticles without any chemical additives. A comparison of the antimicrobial effect of silver/gold nanoparticles and their formulations (hydrogels, ointments, aqueous solutions) showed that both metallic nanoparticles have antibacterial and antibiofilm effects, with silver-based hydrogels having particularly high antibiofilm efficiency. The highest antibacterial and antibiofilm efficacies were obtained against Pseudomonas aeruginosa when using silver nanoparticle hydrogels, with antibiofilm efficacies of over 75% registered. The hydrogels incorporating green nanoparticles displayed a 200% increased bacterial efficiency when compared to the controls and their components. All silver nanoparticle formulations were ecologically obtained by "green synthesis" and were shown to have an antimicrobial effect or potential as keratinocyte-acting pharmaceutical substances for ameliorating infectious psoriasis wounds.

The present study aims to demonstrate the influence of the polymer-carrier type and proportion on the quality performance of newly developed oral immediate-release tablets containing amiodarone solid dispersions obtained by hot-melt extrusion. Twelve solid dispersions including amiodarone and different polymers (PEG 1500, PEG 4000; PEG 8000, Soluplus ® , and Kolliphor ® 188) were developed and prepared by hot-melt extrusion using a horizontal extruder realized by the authors in their own laboratory. Only eleven of the dispersions presented suitable physical characteristics and they were used as active ingredients in eleven tablet formulations that contain the same amounts of the same excipients, varying only in solid dispersion type. The solid dispersions' properties were established by optical microscopy with reflected light, volumetric controls and particle size evaluation. In order to prove that the complex powders have appropriate physical characteristics for the direct compression process, they were subjected to different analyses regarding their flowability and compressibility behavior. Additionally, the Fourier transform infrared spectroscopy and X-ray diffraction analysis were performed on the obtained solid dispersions. After confirming the proper physical attributes for all blends, they were processed into the form of tablets by direct compression technology. The manufactured tablets were evaluated for pharmacotechnical (dimensions-diameter and thickness, mass uniformity, hardness and friability) and in vitro biopharmaceutical (disintegration time and drug release) performances. Furthermore, the influence of the polymer matrix on their quality was determined. The high differences in flow and compression performances of the solid dispersions prove the relevant influence of the polymer type and their concentration-dependent plasticizing properties. The increase in flowability and compressibility characteristics of the solid dispersions could be noticed after combining them with direct compression excipients owning superior mechanical qualities. The influence of the polymer type is best detected in the disintegration test, where the obtained values are quite different between the studied formulations. The use of PEG 1500 alone or combined in various proportions with Soluplus ® leads to rapid disintegration. In contrast, the mixture of PEG 4000 and Poloxamer 188 in equal proportions determined the increase in disintegration time to 120 s. The use of Poloxamer 188 alone and a 3:1 combination of PEG 4000 and Soluplus ® also generates a prolonged disintegration time for the tablets.

Background: Occupational exposure to blood and body fluids has become a serious public health problem for healthcare workers and is a major risk for the transmission of various infections such as human immune-deficiency virus, hepatitis B virus, and hepatitis C virus. This systematic review and meta-analysis aims to determine the career time and previous one-year global pooled prevalence of occupational exposure to blood and body fluids among healthcare workers., Methods: For the review, the articles published in English were searched using the electronic databases (SCOPUS/Science Direct, PubMed, Web of Science, Google Scholar, CINAHL, MEDLINE, Cochrane Library, DOAJ, and MedNar) with a combination of Boolean logic operators (AND, OR, and NOT), Medical Subject Headings (MeSH), and keywords. A quality assessment was conducted to determine the relevance of the articles using JBI critical appraisal tools. Furthermore, several steps of assessment and evaluation were taken to select and analyze the relevant articles., Results: Of the 3912 articles identified through the electronic database search, 33 that met the inclusion criteria were included in the final analysis. The current study found that the global pooled prevalence of blood and body fluids among healthcare workers during career time and in the previous one year accounted for 56.6% (95% CI: 47.3, 65.4) and 39.0% (95% CI: 32.7, 45.7), respectively. Based on subgroup analysis by publication year, survey year, and World Health Organization regions, the highest prevalence of blood and body fluid exposure in the last 12 months was observed among articles published between 2004 and 2008 (66.3%), conducted between 2003 and 2008 (66.6%), and conducted in the Southeast Asia Region (46.9%). The highest career time prevalence was 60.6%, 71.0%, and 68.4% for articles published between 2015 and 2020, conducted between 2015 and 2019, and reported in the African region, respectively., Conclusion: The current study revealed a high prevalence of occupational exposure to blood and body fluids among healthcare workers and suggests the need to improve occupational health and safety services in healthcare systems globally., Competing Interests: The authors declare that there are no conflicts of interest in this work., (Copyright © 2022 Dechasa Adare Mengistu et al.)

According to the current literature, Noninvasive Ventilation (NIV) is a well-recognized respiratory support technique for patients affected by Acute Respiratory Failure (ARF). As highlighted by recent meta-analysis, a tight adherence to protocols regarding patients' selection criteria, relative or absolute contraindications, plus highly skilled and experienced operators, can positively affect the NIV performance and mortality rates. Positive outcome from NIV respiratory support is dependent from: patient's clinical condition and education needs; confidence of the staff with NIV technology; choice and management of the most suitable interface available prevention of interface complications; nutritional assessment (artificial feeding if required) and conditioning of medical gas. Despite these issues, the air leakage represents the major threat during NIV support. Indeed, to obtain a positive outcome from this treatment, the 'NIV troubleshooting' management appears to be crucial. Common issues as air leakage, patient-ventilator asynchrony, interface related pressure ulcers, discomfort, and gastric distention should be promptly detected and solved. The analysis of these current issues reveals a lack of evidence based practice, resulting in bed-side clinical interventions based only on the expert consensus or local opinions. To improve this knowledge gap, more efforts are strongly recommended from medical and nursing research communities. Multicenter randomized controlled clinical trials are needed to achieve adequate knowledge to reach the best patient's outcome. Further information to identify new areas of nursing research on NIV, can be achieved from qualitative studies performed on patients and healthcare operators.

We describe the case of four patients who had undergone breast surgery. The post-operative analgesia consisted in levobupivacaine administered through a catheter placed between the pectoralis minor and the pectoralis major using ultrasound guided technique. The quality of the analgesia was excellent quality. No side-effects were encountered., (Copyright © 2014 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)

Given that the Internet is now a major source of information regarding health and mental health problems, and that it is in the interest of the pharmaceutical industry to influence public and professional opinion, this study evaluated 70 websites about erectile dysfunction. The 31 drug company-funded websites (44%) were, compared with the 39 websites that are not industry funded, significantly more biased toward biological factors in general, and toward medication in particular (p < .01). The high proportion of websites that are industry sponsored, and the bias of those websites, confirms previous studies on depression, posttraumatic stress disorder, schizophrenia, and attention deficit hyperactivity disorder, and demonstrates that drug companies are using their financial might to manipulate public and professional opinion on the Internet.

Aim of Study: Marketplaces epitomize a region's culture and trade, and can give a rapid insight into traditions and salience of commercialized medicinal products. The Qaysari bazaar, bordering the citadel in Erbil city in the Kurdistan Autonomous Region, Iraq, has 21 herbalist shops trading natural medicinal products, wild-crafted and cultivated from all over the Middle East and Asia Minor., Materials and Methods: Freelist surveys were conducted with 18 of these herbalists to determine diversity and salience of traded traditional medicinal plants. Interviews were conducted to document use, trade volume, origin, stock and value of the reported species. Plant species were identified using a combination of morphological identification and molecular barcoding using the ITS region., Results: Vouchers were collected for a total of 158 samples, corresponding to 82 species of plants, 5 animal products, 8 types of stones, minerals or chemicals, as well as 16 mixtures of plant products. Consensus Analysis of the herbalist interviews shows strong support for a single culture of herbalist plant use., Conclusions: Most reported plant species are known to have been used since antiquity, and uses are identical or similar to previously documented uses. Herbalists report a steady year-on-year increase in trade due to the economic stability in recent times. A majority (64%) of medicinal plants is imported from outside Iraq, and the data shows that imported plants trade at a higher price than locally-sourced species, and that these species are stocked in higher volumes by the herbalists to ensure a steady supply to consumers. A strong tradition of herbal medicine exists in Kurdistan today exemplified by the diverse and vigorous trade in medicinal plants commercialized from the provinces around Erbil to countries as far away as India, Spain and Libya., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)